Abstract:
:More than 2million human erythroblasts extrude their nuclei every second in bone marrow under hypoxic conditions (<7% O2). Enucleation requires specific signal transduction pathways and the local assembly of contractile actomyosin rings. However, the energy source driving these events has not yet been identified. We examined whether different O2 environments (hypoxic [5% O2] and normoxic [21% O2] conditions) affected human CD34+ cell erythroblast differentiation. We also investigated the regulatory mechanisms underlying energy production in erythroblasts during terminal differentiation under 5% or 21% O2 conditions. The results obtained revealed that the enucleation ratio and intracellular levels of adenosine triphosphate (ATP), lactate dehydrogenase (LDH) M3H, and hypoxia-inducible factor 1α in erythroblasts during terminal differentiation were higher under the 5% O2 condition than under the 21% O2 condition. We also found that the enzymatic inhibition of glyceraldehyde 3-phosphate dehydrogenase and LDH, key enzymes in anaerobic glycolysis, blocked the proliferation of colony-forming units-erythroid and enucleation of erythroblasts, and also reduced ATP levels in erythroblasts under both hypoxic and normoxic conditions. Under both conditions, phosphorylation of the Ser232, Ser293, and Ser300 residues in pyruvate dehydrogenase (inactive state of the enzyme) in erythroblasts was involved in regulating the pathway governing energy metabolism during erythroid terminal differentiation. This reaction may be mediated by pyruvate dehydrogenase kinase (PDK) 4, the major PDK isozyme expressed in erythroblasts undergoing enucleation. Collectively, these results suggest that ATP produced by anaerobic glycolysis is the main source of energy for human erythroblast enucleation in the hypoxic bone marrow environment.
journal_name
Exp Hematoljournal_title
Experimental hematologyauthors
Goto T,Ubukawa K,Kobayashi I,Sugawara K,Asanuma K,Sasaki Y,Guo YM,Takahashi N,Sawada K,Wakui H,Nunomura Wdoi
10.1016/j.exphem.2019.02.004subject
Has Abstractpub_date
2019-04-01 00:00:00pages
14-26.e1eissn
0301-472Xissn
1873-2399pii
S0301-472X(19)30074-8journal_volume
72pub_type
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journal_title:Experimental hematology
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更新日期:2016-05-01 00:00:00
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journal_title:Experimental hematology
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更新日期:1997-10-01 00:00:00
abstract::The mechanism of localization, migration, and regulation of hematopoiesis at different stages of ontogeny is not well understood, but may relate to the specific adhesive interactions between hematopoietic stem cells and their microenvironment at different ontogenic stages. We studied the expression of cell adhesion mo...
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doi:10.1016/s0301-472x(98)00031-9
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abstract::Immunoenzymatic (IE) staining for antigen detection on intact human bone marrow (BM) colonies grown in agar layers is described. The reliability of this method allowed a study of antigenic changes during myelomonocytic differentiation. Phenotypic analysis was carried out at different times using the following monoclon...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-06-01 00:00:00
abstract::A factor present in normal mouse serum stimulates proliferation of late erythroid precursors grown in cultures in vitro. This factor was shown not to have a corrective effect on culture conditions by the following criteria: (a) CFU-E frequency in the absence of NMS was at least as great as published data for various m...
journal_title:Experimental hematology
pub_type: 杂志文章
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更新日期:1984-08-01 00:00:00
abstract::Germinal center-associated nuclear protein (GANP) is a unique and multifunctional protein that plays a critical role in cell biology, neurodegenerative disorders, immunohematology, and oncogenesis. GANP is an orthologue of Saccharomyces Sac3, one of the components of the transcription export 2 (TREX-2) complex and a m...
journal_title:Experimental hematology
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abstract::This report presents the results of studies using long-term bone marrow cultures (LTBMC) of human bone marrow cells to investigate the effect of HIV-1 on in vitro hematopoiesis. Confluent stromal cell layers established from human bone marrow cells were irradiated to eliminate residual hematopoietic progenitor cells a...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1994-12-01 00:00:00
abstract::An improved negative immunomagnetic selection strategy has been devised for the enrichment of primitive hemopoietic cells using the high proliferative potential colony-forming cell (HPP-CFC) assay as an index of stem cell purification. Immunomagnetic selection was carried out using goat anti-rat conjugated M-450 Dynab...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1991-02-01 00:00:00
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journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(99)00058-2
更新日期:1999-08-01 00:00:00
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journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1992-11-01 00:00:00
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journal_title:Experimental hematology
pub_type: 临床试验,杂志文章
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更新日期:2014-09-01 00:00:00
abstract::The effects of the inhibition of the cyclooxygenase and lipoxygenase metabolic pathways of arachidonic acid on the postirradiation recovery of hematopoietic functions in mice were investigated. Nordihydroguaiaretic acid (NDGA), an inhibitor of prostaglandin (PG) and leukotriene (LT) production, was given to animals in...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract::Seven patients received cancer chemotherapy with high-dose cyclophosphamide (HD-CTX) associated with either recombinant human granulocyte colony-stimulating factor (rhG-CSF), rh interleukin-3 (rhIL-3), rh granulocyte-macrophage CSF (rhGM-CSF) plus rh erythropoietin (rhEpo), rhIL-3 plus rhGM-CSF, or rhIL-3 plus rhG-CSF...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-11-01 00:00:00
abstract::The effect of staurosporine, a novel calcium/phospholipid-dependent protein kinase (protein kinase C) inhibitor, on differentiation of human promyelocytic leukemic HL-60 cells, was investigated. Staurosporine inhibited HL-60-cell proliferation in a concentration-dependent manner, but did not induce HL-60-cell differen...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract::Clonality studies can establish the single-cell origin of tumors and thus differentiate clonal malignant and premalignant processes from reactive polyclonal processes. Detection of clonal cells may be based on direct tracking of cell lineage-specific sequences or disease-specific somatic mutations identifying the clon...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2020.01.013
更新日期:2020-03-01 00:00:00
abstract::A transplanted tumor that induces granulocytosis and produces colony stimulating factor (CSF) was studied in mice during several passages. The sequence of events leading to granulocytosis was characterized. Band granulocytes were increased 3 days after tumor inoculation, while simultaneously CFU-s and CFU-c in bone ma...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1978-04-01 00:00:00
abstract::The relationship between the hematopoietic stem cell (HSC) population and its surrounding bone marrow microenvironment is a rapidly evolving area of research. Normal HSC processes rely heavily on a complex communication network involving various marrow niches. Although leukemogenesis largely results from abnormal gene...
journal_title:Experimental hematology
pub_type: 杂志文章,评审
doi:10.1016/j.exphem.2018.07.001
更新日期:2018-10-01 00:00:00
abstract:OBJECTIVE:The retinoic acid receptors (RARs) alpha, beta2, and gamma regulate specific subsets of target genes during all-trans retinoic acid (RA) induced differentiation of F9 teratocarcinoma stem cells. The Tie1 gene exhibited reduced expression in RA-treated F9 RARgamma-/- cells as compared to wild-type (WT) by micr...
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pub_type: 杂志文章
doi:10.1016/j.exphem.2007.12.016
更新日期:2008-05-01 00:00:00
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journal_title:Experimental hematology
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1995-12-01 00:00:00
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pub_type: 临床试验,杂志文章
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更新日期:2003-06-01 00:00:00
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journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2005.05.007
更新日期:2005-08-01 00:00:00
abstract::The statistical distribution of colony counts in the spleen colony assay was determined in C57BL/6 and C3H mice under varying conditions of the assay procedure. Assay mice were given syngeneic bone marrow cells from normal or irradiated donors. The mice were injected intravenously with marrow cells either immediately ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1977-11-01 00:00:00
abstract::The heterogeneity among progenitor cells of granulocytes and macrophages capable of forming colonies in vitro (CFU-c) is analysed. If specific culture conditions and stimuli are used, it is possible to discriminate among three subpopulations of CFU-c. CFU-c directly responding to CSF prepared from pregnant mouse uteri...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1979-11-01 00:00:00
abstract:OBJECTIVE:Polycythemia rubra vera-1 (PRV-1) is a GPI-linked protein that is expressed on a subgroup of neutrophils. The number of PRV-1-expressing neutrophils increases in pregnancy and sepsis, or after administration of granulocyte colony-stimulating factor. Expression of the PRV-1 gene is also increased in patients w...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2007.09.008
更新日期:2007-11-01 00:00:00
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journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/s0301-472x(00)00652-4
更新日期:2001-02-01 00:00:00
abstract:OBJECTIVE:It has been shown previously that infection with diverse viruses induces alterations in bone marrow lineage-specific progenitor cells. As complications arising from secondary bacterial infections can adversely affect the host, we investigated whether virally induced hematological alterations could contribute ...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2005.09.005
更新日期:2005-12-01 00:00:00
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journal_title:Experimental hematology
pub_type: 杂志文章
doi:10.1016/j.exphem.2008.06.012
更新日期:2008-11-01 00:00:00
abstract::We have established an in vitro system with which to examine the ability of Abelson murine leukemia virus (A-MuLV) to infect early hemopoietic progenitor cells. Blast cell colonies containing less than 100 cells were shown to contain up to 85% of cells with secondary hemopoietic colony-forming ability. Infection of ce...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1988-01-01 00:00:00
abstract::Human cord blood or bone marrow cells expressing the CD34 surface antigen include a population of pluripotent progenitors. We identified and isolated a subpopulation of cells coexpressing CD34 and c-kit, a transmembrane receptor with tyrosine kinase activity. Novel monoclonal antibodies (16A6, 14A3, 3D6) directed agai...
journal_title:Experimental hematology
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00